|Publication number||US4335107 A|
|Application number||US 05/912,829|
|Publication date||Jun 15, 1982|
|Filing date||Jun 5, 1978|
|Priority date||Jun 5, 1978|
|Also published as||DE2967376D1, EP0006695A1, EP0006695B1|
|Publication number||05912829, 912829, US 4335107 A, US 4335107A, US-A-4335107, US4335107 A, US4335107A|
|Inventors||Glenn H. Snoeyenbos, Olga M. Weinack, Charles F. Smyser|
|Original Assignee||Snoeyenbos Glenn H, Weinack Olga M, Smyser Charles F|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (17), Non-Patent Citations (18), Referenced by (58), Classifications (7), Legal Events (3)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to material which inhibits the implantation of salmonella in poultry and to the use of such materials to prevent such implantation in poultry.
The fact that the intestinal microflora of salmonella-free birds inhibits the implantation of salmonella in other birds has been reported. Attention is called to a writing of the present inventors entitled "Protecting Chicks and Poults from Salmonella by oral Administration of `Normal` gut Microflora" (Snoeyenbos et al) Avian Diseases, Vol. 22, No. 2, April-June, 1978, pp. 273-287; the writing and the references therein cited may be used as background for the present disclosure and is drawn upon hereinafter. This writing and the references cited therein are expressly incorporated herein by reference.
The effect of salmonella upon poultry (e.g. chicks and turkey poults) is three-fold; the salmonella acts to infect the poultry; it may be passed to human consumers of the poultry; and it appears in the excrement of the poultry. It is noted in said writing that the resistance of young chicks and turkey poults increased by early administration thereto of microflora in intestinal contents or feces from selected adult chickens. Since poultry forms an important food source, it is of the utmost importance that salmonella infection which endanger human health be eliminated from birds to be used as food. Consequently, poultry flocks which are found to have such infection in some birds are frequently entirely destroyed, at great economic hardship. There is an urgent need for a means of preventing or reducing to a minimum such infection of poultry flocks.
We have found that the administration to young poultry of salmonella implantation resistant avian intestinal microflora obtained from pathogen-free birds forms a safe and effective way to prevent or inhibit the chance of infestation of poultry flocks by paratyphoid salmonella and thus produces a healthy flock of birds capable of safe human consumption as food. We have found, further, that such microflora, in a lyophilized or other dried condition, forms a stable article which can be reconstituted by the poultry grower and so used.
Accordingly, it is an object of the present invention to provide a mixture of avian intestinal microflora which inhibits colonization of paratyphoid salmonella, including arizona groups, in chicks and turkey poults.
Another object is to provide a mixture that is free of known avian and/or human pathogens.
A further object is to provide a method of treating poultry with a mixture of gut microflora that maintains optimum biological protective effect throughout the life of the poultry.
A still further object is to provide a material and method of administering the same, for the protection of a living organism against a specific group of pathogens.
These and still further objects are addressed hereinafter.
Some comments of a general nature are in order to provide a foundation for the more detailed discussion later. While the teachings herein are broader in scope, they are discussed in the context of inhibiting intestinal colonization by salmonella, including the arizona groups, in poultry and, more precisely, chicks and turkey poults (also called "treated birds" herein) by administering to the chicks and turkey poults a mixture of substantially pathogen-free avian intestinal microflora having the property of blocking subsequent colonization by paratyphoid salmonella, including the arizona groups, in the poultry in which the mixture is established. The term paratyphoid salmonella is used to cover the non host-adapted salmonella, and to exclude the host adapted salmonella pullorum and salmonella gallinarum. The dosage administered to the treated birds ideally is an amount which will result in substantially complete exclusion of salmonella from the intestines of the treated birds within about seventy-two hours. A larger dosage hastens the development of such exclusion, a smaller dosage delays the development of such exclusion. Later it is shown that a 1/2 ml. dosage of a 1-4 mixture of fecal material is more than adequate for present purposes.
The original source of microflora to be used in this invention is the fecal droppings of salmonella-free birds which have been tested and found by the known methods in the art to inhibit actively the implantation of salmonella in young chicks. This is then propagated and, at the same time, freed of pathogens by anaerobic culture (in which medium the microflora propagate but the pathogenic viruses do not, thus diluting the virus concentration to minimal).
The actual production of large quantities of the mixture to be administered, as a preventive measure, to young birds, is then effected by establishing this pathogen-free culture in substantially pathogen-free poultry (also called "pathogen-free poultry or birds" herein) within a short time (typically about twenty-four to seventy-two hours) of hatching of the poultry. The fecal droppings of the poultry are collected and the droppings are treated to prevent inactivation thereof. Typically, the treatment is that of lyophilizing the droppings, but they can be maintained at dry ice temperature or liquid nitrogen temperature to prevent inactivation. Also, typically, coarse particulate matter is separated from the droppings and the remainder is cultured anaerobically to increase the population of the active ingredients (i.e., microflora) thereof. It is, then, the cultured microflora that is lypholized or otherwise treated to prevent inactivation.
Terms used herein are employed in their accepted sense and/or are defined. In this connection, various avian pathogens are listed, among other placed, in the publication "Isolation and Identification of Avian Pathogens" published by the American Association of Avian Pathologists. Bergey's Manual of Determinative Bacteriology, 8th Ed. (Backman and Gibbons) Williams and Wilkins, Editors, Baltimore, Maryland, may be used. Reference is made below to pathogen-free (SPF) chicken breeding stock. Such breeding stock may be obtained from SPF type eggs from a number of sources; the eggs used were obtained from SPAFAS, Incorporated, R.F.D. No. 3, Norwich, Connecticut (hereinafter called SPAFAS). Other SPF type eggs and/or chicks are available from Larson Laboratory Eggs, Inc., 1412 Park Street, Box D, Gowrie, Iowa, Truslow Farms, Chester, Pa., and Lohman and Company, Cuxhaven, Germany. The egg groups available are SPF-utility, SPF-cofal and SPF-cofal/Marek; the negative tests applied to each egg group classification is published by the producer. As used herein, the term salmonella is used to denote salmonella groups including the arizona groups which are not host adapted. Especially important are the paratyphoid salmonella, including arizonas.
A culture of the avian microflora described above has been deposted with the American Type Culture Collection (ATCC 31413), and is available for the public in accordance with the provisions of MPEP 608.01(p).
Our invention can be further described and explained by the following examples:
Fresh fecal droppings were collected from donor birds known to have effective microflora and suspended in 4 parts of physiological saline to 1 part by weight of fecal droppings. After removing coarse particulate matter from the droppings by filtration through 4 layers of cheesecloth, 1 ml. portions of the filtrate were transferred to tubes containing 19 ml. of VL broth with 10% fecal extract and 5% liver extract as described by Barnes and Impey (Barnes, E. M., and C. S. Impey, 1970, British Poult. Sco., 11:467-481). The broth was incubated for 96 hours at 37° C. under anaerobic conditions to increase the population of microflora therein. Following incubation, 1 ml. of the broth mixture was removed, diluted with 4 ml. of VL broth and 1 ml. of that mixture was transferred to each of several tubes containing 19 ml. of sterile VL broth which was anaerobically incubated at 37° C. for an additional 96 hours. One additional transfer was made in the same manner which resulted in a 1×106 dilution of the original fecal sample. This serial method of anaerobic culture served to dilute viruses in the original inoculum to the point of extinction while maintaining the original bacterial flora. Following 96 hours of anaerobic incubation of these tubes at 37° C., 0.5 ml. of the cultured mixture was placed by pipette into the crop of each of 50 newly-hatched chicks, that is, chicks within 72 hours of hatching.
The above chicks were progeny of specific pathogen-free breeding stock (SPAFAS, SPF, Cofal/Marek) maintained under rigid isolation and periodically tested by appropriate methods to assure freedom from bacterial and viral pathogens as specified below for testing of these chicks.
Following administration of the VL broth culture, the chicks were placed in wire floored batteries in a room maintained under comprehensive isolation management.
All birds in the group were individually blood sampled at six weeks of age and each serum tested by appropriate serologic tests to assure freedom from antibodies to the following avian pathogens:
Adenoviruses (11 types)
Infectious Bursal Agent
Influenza (Type A)
Egg-drop Adeno-line Virus
Additionally, all birds were determined to be free of non host-adapted salmonella, including arizona groups, by periodic selective enrichment culture of fecal droppings and by similar culture of individual birds.
The entire group of birds was tested at two additional monthly intervals after six weeks by all the above methods. Samples of fecal droppings were collected between the six and ten week test periods for lyophilization or preservation for "seed" inoculum.
Also samples of feces from the group of birds were examined at weekly intervals starting at four weeks of age to assure absence of coccidia and ova of nematodes, trematodes and cestodes. This examination was by standard sugar flotation methods. No special effort was made to detect the possible presence of flagellated protozoa as this group of organisms is unable to withstand lyophilization.
In both Method A and Method B described below it is necessary to use chicks or turkey poults that are known to be free of all salmonella, including the arizona groups. Either Method A or Method B may be used for evaluation.
Each test requires at least one group of 10 one-day-old chicks or turkey poults which are pretreated by administering into the crop by a pipette a standard amount of the selected microflora (usually in 0.5 ml. quantity). The chicks are then placed in a clean starting battery on a new litter in a clean pen and fed and watered. A comparable group not pretreated with microflora is similarly placed in a separate clean room as controls.
After twenty-four hours, chicks (or poults) of the same age are infected with salmonella by administering into the crop approximately 1×105 viable cells from a twenty-four hour broth culture of the test paratyphoid salmonella (either S. typhimurium, S. infantis, or S. enteritidis). Pathogenic strains are used. Two infected birds are added to each test group as "seeder" birds.
All birds in each test group are then individually cultured by cloacal swab at one, two and three weeks of age. Effective protection by microflora used for the original pretreatment is indicated by few or no isolations of salmonella from the pretreated birds and isolation of salmonella from all or substantially all of the control group and from the "seeder" birds.
This test method is started as described under Method A except that the test birds are placed in wire floored starting batteries.
No seeder chicks are introduced, and inserted at seventy-two hours all birds are individually dosed by administering into the crop approximately 1×105 viable cells of the test salmonella previously described under Method A. As this severe challenge may result in pretreated birds shedding salmonella, measurements are made by counting by standard methods viable salmonella in mixed fecal droppings collected from each group of birds. (Use of naladixie acid resistant strains of salmonella for challenge facilitates enumeration.)
The control group that has not been pretreated excrete very large numbers of viable salmonella (1×104 →1×107 or more) cells per gram of wet feces. The pretreated group excrete very few if any viable salmonella (usually less than 1×102) cells per gram of wet feces. Counts are made at three and seven days after challenge.
The avian microflora of the present invention may be established in the gastrointestinal tract of the poultry, for example, by introducing or administering it in water fed to the poultry, internasally as an aerosol or it may be added to feed with precaution against infection. Proper treatment of the newly-hatched birds serves to inhibit the subsequent colonization of the intestinal tract thereof by salmonella, nevertheless, this is as inhibition only and this can be overcome by severe exposure. The avian microflora so administered, it is believed, functions by way of competitive exclusion. It should be noted, also, that the material so administered may also play a role in protecting birds against other enteric infections.
The SPAFAS, SPF-Cofal/Marek flock above mentioned is checked for freedom from the following avian pathogens:
Infectious Bursal Agent
Influenza (Type A)
Lymphoid Leukosis Viruses
Lymphoid Leukosis Antibody
Lymphoid Leukosis Antibody
The term microflora is used above to denote living organisms present in the fecal droppings of poultry. Pathogen-free or substantially pathogen-free avian intestinal microflora means microflora that has an indiscernible amount of pathogens therein, or, at least, an amount that is below a level that will affect birds if introduced thereto in the manner described herein.
Modifications of the invention herein disclosed will occur to persons skilled in the art.
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|U.S. Classification||424/93.3, 426/71, 426/61|
|International Classification||A61K35/74, A01N63/00|
|Mar 29, 1985||AS||Assignment|
Owner name: NURMI, ESKO V. HOPEASALMENTIE 22 00570 HELSINKI,
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:SNOEYENBOS, GLENN, H.;WEINACK, OLGA M.;SMYSER, CHARLES F.;REEL/FRAME:004382/0251
Effective date: 19840813
|Jan 28, 1992||AS||Assignment|
Owner name: ORION-YHTYMA OY A CORPORATION OF FINLAND
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:NURMI, ESKO V.;REEL/FRAME:005990/0501
Effective date: 19920117
|Mar 9, 1993||RR||Request for reexamination filed|
Effective date: 19921230